A Randomized Phase III Study to Assess the Effect of a Longer Duration of Consolidation Treatment With Nilotinib on TFR in CP CML.

NCT ID: NCT01743989

Last Updated: 2021-07-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 620 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-15
• Study Completion Date: 2020-07-08

Brief Summary

This study aimed to assess the optimal duration of nilotinib 300 mg twice daily (BID) consolidation treatment in patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML), in order that patients remained in treatment-free remission (≥MR4.0) without molecular relapse 12 months after starting the Treatment-Free Remission (TFR) phase.

Detailed Description

This was a prospective, randomized, open-label, multicenter Phase III study. The study design was made up of 3 phases:

• Nilotinib induction phase: 12 months
• Nilotinib consolidation phase: 12 or 24 months, depending on randomization
• Nilotinib treatment-free remission (TFR) phase: 24 or 36 months, depending on randomization.

Subjects were enrolled into the study and were treated with nilotinib 300mg twice daily (BID) for 24 months, during the induction (12 months) and consolidation (12 months) phases. At the end of the first 24 months of treatment, participants achieving a sustained molecular response (defined as ≥ MR4.0, in 4 out of 5 real-time quantitative polymerase chain reaction (RQ-PCR) assessments, including the last assessment, in the last 12 months) were randomized on a 1:1 basis to either:

1. suspend nilotinib treatment immediately and enter the TFR phase for 36 months (Nilotinib 24-month treatment arm), or

2. continue nilotinib treatment for a further 12 months (post-randomization consolidation phase), then suspend treatment and enter the TFR phase for 24 months (Nilotinib 36-month treatment arm).

Participants not achieving a sustained molecular response at 24 months from treatment start were not eligible for randomization and were treated at the discretion of the investigator according to standard practice. Information on survival, stem cell transplantation, and status of the patient's disease was collected until death or until 5 years from study entry, whichever came first. Additionally, for Nilotinib 36-month treatment arm, participants who did not achieve a sustained molecular response at 36 months from treatment start, discontinued from the study and were treated according to standard practice and followed up until death or until 5 years from study entry, whichever came first.

Participants relapsing during the TFR phase entered the nilotinib re-treatment phase of the study, and were re-treated with the same dose of nilotinib as they were on before the TFR phase. These patients remained on study until the completion of the 5-year study period unless prematurely withdrawn and discontinued from the study for any reason specified in the Protocol.

Conditions

Philadelphia Chromosome Positive (PH+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nilotinib 24-month treatment

Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase

Group Type: EXPERIMENTAL

Nilotinib

Intervention Type: DRUG

Participants received a daily oral nilotinib dose of 300 mg BID, given as two 150 mg capsules BID.

Nilotinib 36-month treatment

Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase

Group Type: EXPERIMENTAL

Nilotinib

Intervention Type: DRUG

Participants received a daily oral nilotinib dose of 300 mg BID, given as two 150 mg capsules BID.

Not randomized

Participants were treated with nolotinib 300mg BID for 24 months, but did not achieve a sustained molecular response after 24 months of treatment.

Group Type: EXPERIMENTAL

Nilotinib

Intervention Type: DRUG

Participants received a daily oral nilotinib dose of 300 mg BID, given as two 150 mg capsules BID.

Interventions

Nilotinib

Participants received a daily oral nilotinib dose of 300 mg BID, given as two 150 mg capsules BID.

Intervention Type: DRUG

Other Intervention Names

AMN107

Eligibility Criteria

Inclusion Criteria

• Confirmed diagnosis of chronic phase Ph+ CML
• Previous first-line treatment with imatinib for a minimum of 2 years;
• Patient in complete cytogenetic response;

Exclusion Criteria

• Previous achievement of MR4.0 at study entry;
• Previous treatment with other target cells inhibitors other than imatinib;
• Patients with any history of detectable atypical Leukemia transcripts or patients with detectable atypical leukemia transcripts at screening;
• Previous anticancer agents for Chronic myeloid leukemia other than imatinib except for cytoreduction;
• Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol;
• History of other active malignancies within the 5 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively;
• Patients who have not recovered from prior surgery;
• Treatment with other investigational agents within 4 weeks of Day 1;
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Linz, Upper Austria, Austria

Novartis Investigative Site

Graz, , Austria

Novartis Investigative Site

Linz, , Austria

Novartis Investigative Site

Linz, , Austria

Novartis Investigative Site

Rankweil, , Austria

Novartis Investigative Site

Salzburg, , Austria

Novartis Investigative Site

Brussels, , Belgium

Novartis Investigative Site

Liège, , Belgium

Novartis Investigative Site

Pleven, , Bulgaria

Novartis Investigative Site

Plovdiv, , Bulgaria

Novartis Investigative Site

Sofia, , Bulgaria

Novartis Investigative Site

Sofia, , Bulgaria

Novartis Investigative Site

Varna, , Bulgaria

Novartis Investigative Site

Brno Bohunice, Czech Republic, Czechia

Novartis Investigative Site

Hradec Králové, CZE, Czechia

Novartis Investigative Site

Holstebro, , Denmark

Novartis Investigative Site

Roskilde, , Denmark

Novartis Investigative Site

HUS Helsinki, , Finland

Novartis Investigative Site

Bayonne, Bayonne Cedex, France

Novartis Investigative Site

Le Mans, Cedex 09, France

Novartis Investigative Site

Paris, Cedex 10, France

Novartis Investigative Site

Caen, Cedex, France

Novartis Investigative Site

Angers, , France

Novartis Investigative Site

Bordeaux, , France

Novartis Investigative Site

Bordeaux, , France

Novartis Investigative Site

Chalon-sur-Saône, , France

Novartis Investigative Site

Chambéry, , France

Novartis Investigative Site

Clermont-Ferrand, , France

Novartis Investigative Site

Corbeil-Essonnes, , France

Novartis Investigative Site

Dunkirk, , France

Novartis Investigative Site

Grenoble, , France

Novartis Investigative Site

La Roche-sur-Yon, , France

Novartis Investigative Site

Lille, , France

Novartis Investigative Site

Lille, , France

Novartis Investigative Site

Lyon, , France

Novartis Investigative Site

Marseille, , France

Novartis Investigative Site

Metz, , France

Novartis Investigative Site

Metz, , France

Novartis Investigative Site

Mulhouse, , France

Novartis Investigative Site

Nice, , France

Novartis Investigative Site

Paris, , France

Novartis Investigative Site

Perpignan, , France

Novartis Investigative Site

Pontoise, , France

Novartis Investigative Site

Rouen, , France

Novartis Investigative Site

Saint-Priest-en-Jarez, , France

Novartis Investigative Site

Toulouse, , France

Novartis Investigative Site

Mannheim, Baden-Wurttemberg, Germany

Novartis Investigative Site

Augsburg, , Germany

Novartis Investigative Site

Bayreuth, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Braunschweig, , Germany

Novartis Investigative Site

Bremen, , Germany

Novartis Investigative Site

Chemnitz, , Germany

Novartis Investigative Site

Cologne, , Germany

Novartis Investigative Site

Dresden, , Germany

Novartis Investigative Site

Eisenach, , Germany

Novartis Investigative Site

Frankfurt, , Germany

Novartis Investigative Site

Georgsmarienhütte, , Germany

Novartis Investigative Site

Halle, , Germany

Novartis Investigative Site

Hamm, , Germany

Novartis Investigative Site

Kiel, , Germany

Novartis Investigative Site

Leipzig, , Germany

Novartis Investigative Site

Lütten Klein, , Germany

Novartis Investigative Site

Magdeburg, , Germany

Novartis Investigative Site

Marburg, , Germany

Novartis Investigative Site

München, , Germany

Novartis Investigative Site

Münster, , Germany

Novartis Investigative Site

Nuremberg, , Germany

Novartis Investigative Site

Offenburg, , Germany

Novartis Investigative Site

Potsdam, , Germany

Novartis Investigative Site

Rostock, , Germany

Novartis Investigative Site

Rostock, , Germany

Novartis Investigative Site

Schorndorf, , Germany

Novartis Investigative Site

Schwäbisch Hall, , Germany

Novartis Investigative Site

Stuttgart, , Germany

Novartis Investigative Site

Velbert, , Germany

Novartis Investigative Site

Westerstede, , Germany

Novartis Investigative Site

Wiesbaden, , Germany

Novartis Investigative Site

Würzburg, , Germany

Novartis Investigative Site

Athens, GR, Greece

Novartis Investigative Site

Thessaloniki, GR, Greece

Novartis Investigative Site

Athens, , Greece

Novartis Investigative Site

Athens, , Greece

Novartis Investigative Site

Pátrai, , Greece

Novartis Investigative Site

Budapest, , Hungary

Novartis Investigative Site

Debrecen, , Hungary

Novartis Investigative Site

Szeged, , Hungary

Novartis Investigative Site

Alessandria, AL, Italy

Novartis Investigative Site

Ancona, AN, Italy

Novartis Investigative Site

Avellino, AV, Italy

Novartis Investigative Site

Bari, BA, Italy

Novartis Investigative Site

Bologna, BO, Italy

Novartis Investigative Site

Brescia, BS, Italy

Novartis Investigative Site

Cagliari, CA, Italy

Novartis Investigative Site

Cremona, CR, Italy

Novartis Investigative Site

Catania, CT, Italy

Novartis Investigative Site

Cona, FE, Italy

Novartis Investigative Site

San Giovanni Rotondo, FG, Italy

Novartis Investigative Site

Florence, FI, Italy

Novartis Investigative Site

Genova, GE, Italy

Novartis Investigative Site

Rome, Lazio, Italy

Novartis Investigative Site

Lecce, LE, Italy

Novartis Investigative Site

Livorno, LI, Italy

Novartis Investigative Site

Messina, ME, Italy

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Modena, MO, Italy

Novartis Investigative Site

Palermo, PA, Italy

Novartis Investigative Site

Palermo, PA, Italy

Novartis Investigative Site

Padua, PD, Italy

Novartis Investigative Site

Pescara, PE, Italy

Novartis Investigative Site

Pisa, PI, Italy

Novartis Investigative Site

Parma, PR, Italy

Novartis Investigative Site

Pavia, PV, Italy

Novartis Investigative Site

Potenza, PZ, Italy

Novartis Investigative Site

Reggio Calabria, RC, Italy

Novartis Investigative Site

Reggio Emilia, RE, Italy

Novartis Investigative Site

Roma, RM, Italy

Novartis Investigative Site

Roma, RM, Italy

Novartis Investigative Site

Roma, RM, Italy

Novartis Investigative Site

Pagani, SA, Italy

Novartis Investigative Site

Siena, SI, Italy

Novartis Investigative Site

Taranto, TA, Italy

Novartis Investigative Site

Orbassano, TO, Italy

Novartis Investigative Site

Torino, TO, Italy

Novartis Investigative Site

Treviso, TV, Italy

Novartis Investigative Site

Udine, UD, Italy

Novartis Investigative Site

Mirano, VE, Italy

Novartis Investigative Site

Venezia, VE, Italy

Novartis Investigative Site

Vicenza, VI, Italy

Novartis Investigative Site

Verona, VR, Italy

Novartis Investigative Site

Napoli, , Italy

Novartis Investigative Site

Novara, , Italy

Novartis Investigative Site

Perugia, , Italy

Novartis Investigative Site

Bergen, , Norway

Novartis Investigative Site

Oslo, , Norway

Novartis Investigative Site

Chorzów, , Poland

Novartis Investigative Site

Gdansk, , Poland

Novartis Investigative Site

Katowice, , Poland

Novartis Investigative Site

Krakow, , Poland

Novartis Investigative Site

Olsztyn, , Poland

Novartis Investigative Site

Opole, , Poland

Novartis Investigative Site

Torun, , Poland

Novartis Investigative Site

Warsaw, , Poland

Novartis Investigative Site

Warsaw, , Poland

Novartis Investigative Site

Lisbon, , Portugal

Novartis Investigative Site

Lisbon, , Portugal

Novartis Investigative Site

Porto, , Portugal

Novartis Investigative Site

Porto, , Portugal

Novartis Investigative Site

Porto, , Portugal

Novartis Investigative Site

Bucharest, District 2, Romania

Novartis Investigative Site

Bucharest, , Romania

Novartis Investigative Site

Bucharest, , Romania

Novartis Investigative Site

Cluj-Napoca, , Romania

Novartis Investigative Site

Iași, , Romania

Novartis Investigative Site

Sibiu, , Romania

Novartis Investigative Site

Timișoara, , Romania

Novartis Investigative Site

Belgrade, , Serbia

Novartis Investigative Site

Belgrade, , Serbia

Novartis Investigative Site

Niš, , Serbia

Novartis Investigative Site

Novi Sad, , Serbia

Novartis Investigative Site

Bratislava, , Slovakia

Novartis Investigative Site

Martin, , Slovakia

Novartis Investigative Site

Ljubljana, , Slovenia

Novartis Investigative Site

Granada, Andalusia, Spain

Novartis Investigative Site

Jaén, Andalusia, Spain

Novartis Investigative Site

Málaga, Andalusia, Spain

Novartis Investigative Site

Seville, Andalusia, Spain

Novartis Investigative Site

Seville, Andalusia, Spain

Novartis Investigative Site

Palma de Mallorca, Balearic Islands, Spain

Novartis Investigative Site

Sabadell, Barcelona, Spain

Novartis Investigative Site

Donostia / San Sebastian, Basque Country, Spain

Novartis Investigative Site

León, Castille and León, Spain

Novartis Investigative Site

Salamanca, Castille and León, Spain

Novartis Investigative Site

Valladolid, Castille and León, Spain

Novartis Investigative Site

Badalona, Catalonia, Spain

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Girona, Catalonia, Spain

Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, Spain

Novartis Investigative Site

Tarragona, Catalonia, Spain

Novartis Investigative Site

Cáceres, Extremadura, Spain

Novartis Investigative Site

A Coruña, Galicia, Spain

Novartis Investigative Site

Pontevedra, Galicia, Spain

Novartis Investigative Site

Santiago de Compostela, Galicia, Spain

Novartis Investigative Site

Pamplona, Navarre, Spain

Novartis Investigative Site

Alicante, Valencia, Spain

Novartis Investigative Site

Alzira, Valencia, Spain

Novartis Investigative Site

Valencia, Valencia, Spain

Novartis Investigative Site

Granollers, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Murcia, , Spain

Novartis Investigative Site

Santa Cruz de Tenerife, , Spain

Novartis Investigative Site

Zaragoza, , Spain

Novartis Investigative Site

Stockholm, , Sweden

Novartis Investigative Site

East Yorkshire, , United Kingdom

Novartis Investigative Site

Edinburgh, , United Kingdom

Novartis Investigative Site

London, , United Kingdom

Novartis Investigative Site

London, , United Kingdom

Countries

Austria; Belgium; Bulgaria; Czechia; Denmark; Finland; France; Germany; Greece; Hungary; Italy; Norway; Poland; Portugal; Romania; Serbia; Slovakia; Slovenia; Spain; Sweden; United Kingdom

References

Borghi L, Rosti G, Maggi A, Breccia M, Di Bona E, Iurlo A, La Barba G, Sportoletti P, Albano F, Galimberti S, Rivellini F, Cambrin GR, Capodanno I, Cuneo A, Bonifacio M, Sica S, Arcaini L, Capochiani E, Minotto C, Ciceri F, Crugnola M, Di Caprio L, Supekar S, Elena C, Baccarani M, Vegni E. Perspectives and Emotional Experiences of Patients With Chronic Myeloid Leukemia During ENESTPath Clinical Trial and Treatment-Free Remission: Rationale and Protocol of the Italian Substudy. Front Oncol. 2021 May 26;11:638689. doi: 10.3389/fonc.2021.638689. eCollection 2021.

Reference Type: DERIVED

PMID: 34123791 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2012-005124-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CAMN107AIC05

Identifier Type: -

Identifier Source: org_study_id